Carcinoembryonic Antigen, a Human Tumor Marker, Cooperates with Myc and Bcl-2 in Cellular Transformation

Carcinoembryonic antigen (CEA) is a tumor marker that is overexpressed in many human cancers and functions in vitro as a homotypic intercellular adhesion molecule. We have investigated the possibility of synergy between CEA, v-Myc, and Bcl-2 in the transformation of cells with differentiation capacity. We find that v-Myc increases the cell division rate and maximum density of rat L6 myoblasts but also markedly stimulates both apoptosis and surprisingly, differentiation, thus preventing transformation. The superposition of Bcl-2 blocks the apoptotic stimulation of v-Myc and independently promotes further cell division at confluence, but still allows differentiation. The further expression of CEA has a dominant effect in blocking differentiation, regardless of the presence of the other activated oncogenes, generating cells that enter a reversible quiescent G₀-like state in medium promoting differentiation. Transfectants expressing CEA with or without v-myc and bcl-2 allow the emergence of cells with the property of heritable, efficient, anchorageindependent growth in soft agar and the ability to markedly reduce the latency for tumor formation in nude mice. We propose that by prolonging cell survival in the presence of differentiation signals, CEA represents a novel class of dominant differentiation-blocking oncogene.